The interferons are cytokines exhibiting antiviral, antitumor and immunomodulatory effects. At the molecular level these biological effects are the result of a chain of intracellular events, which is triggered outside the cell by the interaction of the ligand with specific transmembrane receptors. Interferon-g (IFN-g) is a 31kD homodimer. It binds two distinct receptors: the a-chain and the b-chain, to form a complex with the stoichiometry 1:2:2, one dimeric ligand and two copies of each receptor. The structure of a 1:2 complex (dimeric ligand and two a-chains) has been determined to about 3 _ resolution (MR Walter, WT Windsor, TL Naganbhushan, DJ Lundelll, kCA Lunn, PJ Zauodny, SK Narula, Nature 376:230, 1995; SE Ealick personal communication). We have constructed a single-chain IFN-g, which only binds a single a-chain ECD. These crystals diffract to 2 _ resolution. We collected 2 _ data a beam line A1 last month. A molecular replacement solution was obtained. There are two copies of the receptor complex in the asymmetric unit. Refinement has been initiated withthe 89,000 unique data. The current R value is 26% and the maps reveal significant detail in the protein structure and the solvation model.